Illustrations by Chris Gash

Nature and nurture both matter in the move to personalized medicine.

In some not-too-distant future, your health risks and medical problems may be investigated and pieced together like crime scenes. Your health care provider will collect key evidence: urine, blood and DNA samples. You’ll be questioned about where you live, work and travel, and what you eat, drink and do.

Your relatives, too, will be investigated—not personally, of course, but their medical histories and genetic data will be scoured for additional clues.

The information will be given to the detectives in this future scenario: software programs equipped with smart algorithms. What will it mean for you?

A shift to this kind of data-driven, individualized health care is a lofty aim. It promises a more complete picture of what promotes health versus disease in any given person.

USC researchers are moving closer to that. Through studies that compare health outcomes across ethnicities and races and between genders, they’re piecing together the factors that raise or lower disease risk.

Their findings will help future clinicians interpret each patient’s information to practice truly “personalized” medicine. Some patients are already seeing the benefits today.

Getting Personal

When you look at their DNA, any two random people will appear more than 99 percent identical. But they can differ at about 3 million positions along the DNA sequence. Understanding these differences and how they interact with factors such as diet, environment and behavior is what will make medicine personal.

“A disease may not be caused by a single gene mutation, but rather by a combination of genetics, behavior, socioeconomic situation, and other underlying issues we’re just beginning to understand,” says USC Roski Eye Institute Director Rohit Varma, who studies how eye disease affects different ethnic and racial groups.

In a recent study, Varma’s team found that Latinos with significant Native American roots who have Type 2 diabetes face an 87 percent higher risk of vision-threatening diabetic retinopathy than the general population. He suspects that their Native American ancestry represents a genetic variant that, combined with lifestyle factors, raises the risk. Consider the Pima Indians, who have high rates of diabetes. In contemporary life, many in this community of former hunters and explorers have become more sedentary and eat a diet full of fast food. These lifestyle changes have contributed to diabetes risk with all of its complications, Varma says.

Another study led by Varma’s team showed that African-Americans have more than double the risk for diabetic macular edema, which can lead to blindness. With such a high risk, it’s vital to detect macular edema early in this population to successfully treat it, Varma says, but disparities in African-Americans’ access to medical care often keep patients from getting the necessary vision screenings and preventive treatment.

“We have good drugs to treat this, so if someone comes in and gets regular eye care, that person should not lose their vision,” he says. “But even though many people have insurance, they are unable to see a physician because they can’t afford their copayments.”

Battles of the Sexes

Men and women also can have different risks of disease tied to factors like diet and behavior, as well as their own genes and anatomy. Recent USC research points out that learning more about the interplay between gender, ethnicity and diet may help doctors find more effective disease screening, prevention and treatment for patients.

In a study of nearly 7,500 adult women, USC researchers noted links between breast cancer, race and ethnicity, and diet. They found that Latinas who ate 20 grams of processed meat per day (equal to a strip of bacon) had a 42 percent higher risk of breast cancer than Latinas who ate little to no processed meat. In contrast, for Caucasian women in the study, eating tuna posed more of a breast cancer risk. In fact, a thimble-sized serving of tuna per day was enough to raise their breast cancer risk by 25 percent. No one is sure yet why.

Hormones, too, can affect health risks differently between men and women. While many people know that estrogen exposure over a lifetime can increase a woman’s breast cancer risk, fewer probably know that the same hormone reduces kidney cancer risk. (Yes, men have estrogen too—just at lower levels than women do.)

Urologist Inderbir Gill, chair and professor in the Catherine and Joseph Aresty Department of Urology, explains that estrogen levels drop in women as they age, but estrogen levels rise in men as they get older. And that rise in estrogen seems to impact senior men when it comes to kidney cancer.

“If a younger woman has a kidney tumor, it is likely benign, whereas in younger men, it likely is cancer. As

Heart disease offers insight into gender’s effects, too. Differences in anatomy and behavior affect outcomes for men and women with cardiovascular issues.

“Women have smaller coronary arteries than men, and tend to have more extensive coronary artery disease, which makes treatment more complicated,” says Vivian Mo, director of the Women’s Cardiovascular Center of USC.

And unlike men who arrive at the local hospital with classic chest pain when they’re having a heart attack, women often ignore their symptoms, which can be as vague as throat tightness and nausea. “By the time they reach the ER, they may have already sustained a fair amount of heart muscle damage, which can lead to future episodes of congestive heart failure,” Mo says.

Although early diagnosis and screening for risk factors such as diabetes and high blood pressure could help, women tend to delay their care and put others’ needs first. After a recent screening event at the Women’s Cardiovascular Center, only 10 percent of women exhibiting key risk factors for heart disease followed up with a physician for preventive care.

“Even though heart disease claims more lives than the top five cancers combined, women are more aware of breast cancer and will seek out screening and treatment for that,” Mo says.

Tailoring Treatment

Researchers believe that collecting information from vast numbers of patients will turn up important clues to how cancer starts and how it can better be treated. Patients at the USC Norris Comprehensive Cancer Center already benefit from data collection focusing on cancer risk factors and incidence across ethnicities and genders. Doctors can apply findings both to cancer treatment and genetic screening for cancer risk.

“We develop customized treatments for each patient that reflect the full complexity of who they are—not just ancestry or gender, but also their medical history, social situation and risk factors, as well as the best evidence from our clinical trials research,” says Stephen Gruber, director of the USC Norris Comprehensive Cancer Center. “We can integrate all of those things into computer models that calculate the risks and benefits of specific diagnostic and therapeutic approaches. We also can tailor our prevention strategies by understanding a patient’s cancer risk and what interventions we can use to modify those risks.”

In some ways, the cancer center was built on this idea. Gruber credits the center’s position as a leader in understanding disparities and treatment options to two pioneering Keck School of Medicine of USC initiatives: the Los Angeles Cancer Surveillance Program founded in 1972 and the Multiethnic Cohort study founded in 1993. The Cancer Surveillance Program records data on every cancer case reported in Los Angeles County, which boasts an ethnically diverse population of about 10 million people. The Multiethnic Cohort study is a long-term, population-based study of more than 215,000 people of African-American, Japanese, Latino, Native Hawaiian and Caucasian origin that examines the relationships between cancer and factors such as genetics, diet and nutrition.

Researchers nationwide use data from both programs to analyze incidence patterns and potential causes of cancer.

“If you want to understand the pattern of cancer in all of us, we are the sole source,” says Cancer Surveillance Program Director Dennis Deapen. “The Los Angeles area’s diverse population enables us to produce ethnicity data that you won’t find in most of the country.”

Drawing on more than 1.3 million cancer cases, the program also helps point out therapies that are more effective for specific kinds of patients over the years.

“Patients and physicians have to make decisions at a given point in time and go with it,” Deapen says. “We’re the people who can look at the data 10 years later and say, ‘For this kind of cancer patient, this treatment worked a whole lot better than that one.’”

Decoding Disease

Sometimes researchers start with genes and then study how they interact with other factors to get a clearer picture of individual health risks and preventive measures.

Keck School of Medicine genetic epidemiologist Chris Haiman co-leads a study to look for gene variations that might explain the uneven risks for conditions such as heart disease and cancer among different groups. Through the study of some 50,000 DNA samples from people of African, Latino and Asian ancestries, the scientists are investigating everything from waist-to-hip measurements (body shape) to the effects of inflammation—and then linking these factors to variations in genes.

“Our hope and expectation is to identify all of the genetic variants involved in disease,” Haiman says.
If Haiman and his colleagues are successful, you might someday take a genetic test that screens for all known diseases rather than just answer questions about family history to determine your risks. Those results will then be considered alongside information about your diet, where you live and work, and even how much exercise and sleep you get. This combined picture will empower you and your doctor to discuss the lifestyle changes and treatment options to keep you healthy.

“Are we there yet? No, we’re not,” Haiman says. “But that’s the goal.”

by Koren Wetmore